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May 29, 2020 by APA Psychiatric News Alert

Potential Risk of Clozapine Toxicity May Occur in Patients With COVID-19

case report in Schizophrenia Bulletin suggests that patients who are taking clozapine may be at risk of clozapine toxicity if they become infected with COVID-19. Clozapine is considered the best option for patients with treatment-resistant schizophrenia, but patients taking the medication are at heightened risk of a rare but serious condition known as neutropenia, which can increase risk of severe infections.

In the Schizophrenia Bulletin report, Thomas Cranshaw, M.B.B.S., and Thiyyancheri Harikumar, M.B.B.S., of Cumbria, Northumberland, Tyne, and Wear NHS Foundation Trust in England, described a 38-year-old man in an inpatient unit who was taking “325 mg per day of clozapine for organic psychosis” who became infected by COVID-19. The authors noted that after the initial emergence of COVID-19 symptoms (coughing, headache, and reduced oxygen saturation), the patient “was drowsy, with markedly increased hypersalivation and myoclonus.”

A blood test revealed the patient’s clozapine levels to be 0.73 mg/l, norclozapine 0.31 mg/l, which the authors noted was “substantially above the patient’s previous stable baseline of 0.57 mg/l, norclozapine 0.22 mg/l.” They added, “The most likely explanation is precipitation of clozapine toxicity by COVID-19 infection. Mechanisms for increase in plasma clozapine during infection have been shown to involve cytokine release downregulating the metabolism of clozapine in the P450 system through CYP 1A2.”

The patient’s clozapine was stopped, and he recovered from COVID-19; however, he experienced some psychotic symptoms during the temporary clozapine cessation, according to the authors.

“This case demonstrates the importance of full clinical assessment of suspected COVID-19 infection in clozapine-treated patients, including assessment for features of pneumonia, clozapine toxicity, clozapine level, and full blood count. Consideration should be given to dose reduction during infection,” Cranshaw and Harikumar concluded. “The risks posed by clozapine treatment during the COVID-19 pandemic must, however, be balanced against the substantial benefit many patients receive from this medication and the likelihood of mental health deterioration with unplanned treatment cessation.”

The Food and Drug Administration has posted guidance for health care professionals regarding certain Risk Evaluation and Mitigation Strategy (REMS)–required laboratory testing during the COVID-19 public health emergency.

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